Augmenting Prediction of Intracranial Aneurysms' Risk Status Using Velocity-Informatics: Initial Experience.

Our primary goal here is to demonstrate that innovative analytics of aneurismal velocities, named velocity-informatics, enhances intracranial aneurysm (IA) rupture status prediction. 3D computer models were generated using imaging data from 112 subjects harboring anterior IAs (4-25 mm; 44 ruptured and 68 unruptured). Computational fluid dynamics simulations and geometrical analyses were performed. Then, computed 3D velocity vector fields within the IA dome were processed for velocity-informatics. Four machine learning methods (support vector machine, random forest, generalized linear model, and GLM with Lasso or elastic net regularization) were employed to assess the merits of the proposed velocity-informatics. All 4 ML methods consistently showed that, with velocity-informatics metrics, the area under the curve and prediction accuracy both improved by approximately 0.03. Overall, with velocity-informatics, the support vector machine's prediction was most promising: an AUC of 0.86 and total accuracy of 77%, with 60% and 88% of ruptured and unruptured IAs being correctly identified, respectively.

Can we explain machine learning-based prediction for rupture status assessments of intracranial aneurysms?

Although applying machine learning (ML) algorithms to rupture status assessment of intracranial aneurysms (IA) has yielded promising results, the opaqueness of some ML methods has limited their clinical translation. We presented the first explainability comparison of six commonly used ML algorithms: multivariate logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), multi-layer perceptron neural network (MLPNN), and Bayesian additive regression trees (BART). A total of 112 IAs with known rupture status were selected for this study. The ML-based classification used two anatomical features, nine hemodynamic parameters, and thirteen morphologic variables. We utilized permutation feature importance, local interpretable model-agnostic explanations (LIME), and SHapley Additive exPlanations (SHAP) algorithms to explain and analyze 6 Ml algorithms. All models performed comparably: LR area under the curve (AUC) was 0.71; SVM AUC was 0.76; RF AUC was 0.73; XGBoost AUC was 0.78; MLPNN AUC was 0.73; BART AUC was 0.73. Our interpretability analysis demonstrated consistent results across all the methods; i.e., the utility of the top 12 features was broadly consistent. Furthermore, contributions of 9 important features (aneurysm area, aneurysm location, aneurysm type, wall shear stress maximum during systole, ostium area, the size ratio between aneurysm width, (parent) vessel diameter, one standard deviation among time-averaged low shear area, and one standard deviation of temporally averaged low shear area less than 0.4 Pa) were nearly the same. This research suggested that ML classifiers can provide explainable predictions consistent with general domain knowledge concerning IA rupture. With the improved understanding of ML algorithms, clinicians' trust in ML algorithms will be enhanced, accelerating their clinical translation.

Arterial Collapse during Thrombectomy for Stroke: Clinical Evidence and Experimental Findings in Human Brains and In Vivo Models.

BACKGROUND AND PURPOSE: Aspiration thrombectomy has become a preferred approach to recanalize large-vessel occlusion in stroke with a growing trend toward using larger-bore catheters and stronger vacuum pumps. However, the mechanical response of the delicate cerebral arteries to aspiration force has not been evaluated. Here, we provide preclinical and clinical evidence of intracranial arterial collapse in aspiration thrombectomy. MATERIALS AND METHODS: We presented a clinical case of arterial collapse with previously implanted flow diverters. We then evaluated the effect of vacuum with conventional aspiration catheters (with and without stent retrievers) in a rabbit model (n = 3) using fluoroscopy and intravascular optical coherence tomography. Then, in a validated human cadaveric brain model, we conducted 168 tests of direct aspiration thrombectomy following an experimental design modifying the catheter inner diameter (0.064 inch, 0.068 inch, and 0.070 inch), cerebral perfusion pressures (mean around 60 and 90 mm Hg), and anterior-versus-posterior circulation. Arterial wall response was recorded and graded via direct transluminal observation. RESULTS: Arterial collapse was observed in both the patient and preclinical experimental models. In the human brain model, arterial collapse was observed in 98% of cases in the M2 and in all the cases with complete proximal flow arrest. A larger bore size of the aspiration catheter, a lower cerebral perfusion pressure, and the posterior circulation in comparison with the anterior circulation were associated with a higher probability of arterial collapse. CONCLUSIONS: Arterial collapse does occur during aspiration thrombectomy and is more likely to happen with larger catheters, lower perfusion pressure, and smaller arteries.

Radiation-Induced Imaging Changes and Cerebral Edema following Stereotactic Radiosurgery for Brain AVMs.

BACKGROUND AND PURPOSE: T2 signal and FLAIR changes in patients undergoing stereotactic radiosurgery for brain AVMs may occur posttreatment and could result in adverse radiation effects. We aimed to evaluate outcomes in patients with these imaging changes, the frequency and degree of this response, and factors associated with it. MATERIALS AND METHODS: Through this retrospective cohort study, consecutive patients treated with stereotactic radiosurgery for brain AVMs who had at least 1 year of follow-up MR imaging were identified. Logistic regression analysis was used to evaluate predictors of outcomes. RESULTS: One-hundred-sixty AVMs were treated in 148 patients (mean, 35.6 years of age), including 42 (26.2%) pediatric AVMs. The mean MR imaging follow-up was 56.5 months. The median Spetzler-Martin grade was III. The mean maximal AVM diameter was 2.8 cm, and the mean AVM target volume was 7.4 mL. The median radiation dose was 16.5 Gy. New T2 signal and FLAIR hyperintensity were noted in 40% of AVMs. T2 FLAIR volumes at 3, 6, 12, 18, and 24 months were, respectively, 4.04, 55.47, 56.42, 48.06, and 29.38 mL Radiation-induced neurologic symptoms were encountered in 34.4%. In patients with radiation-induced imaging changes, 69.2% had new neurologic symptoms versus 9.5% of patients with no imaging changes (P = .0001). Imaging changes were significantly associated with new neurologic findings (P < .001). Larger AVM maximal diameter (P = .04) and the presence of multiple feeding arteries (P = .01) were associated with radiation-induced imaging changes. CONCLUSIONS: Radiation-induced imaging changes are common following linear particle accelerator-based stereotactic radiosurgery for brain AVMs, appear to peak at 12 months, and are significantly associated with new neurologic findings.

Quantitative analysis of flow vortices: differentiation of unruptured and ruptured medium-sized middle cerebral artery aneurysms.

BACKGROUND: Surgical intervention for unruptured intracranial aneurysms (IAs) carries inherent health risks. The analysis of "patient-specific" IA geometric and computational fluid dynamics (CFD) simulated wall shear stress (WSS) data has been investigated to differentiate IAs at high and low risk of rupture to help clinical decision making. Yet, outcomes vary among studies, suggesting that novel analysis could improve rupture characterization. The authors describe a CFD analytic method to assess spatiotemporal characteristics of swirling flow vortices within IAs to improve characterization. METHODS: CFD simulations were performed for 47 subjects harboring one medium-sized (4-10 mm) middle cerebral artery (MCA) aneurysm with available 3D digital subtraction angiography data. Alongside conventional indices, quantified IA flow vortex spatiotemporal characteristics were applied during statistical characterization. Statistical supervised machine learning using a support vector machine (SVM) method was run with cross-validation (100 iterations) to assess flow vortex-based metrics' strength toward rupture characterization. RESULTS: Relying solely on vortex indices for statistical characterization underperformed compared with established geometric characteristics (total accuracy of 0.77 vs 0.80) yet showed improvements over wall shear stress models (0.74). However, the application of vortex spatiotemporal characteristics into the combined geometric and wall shear stress parameters augmented model strength for assessing the rupture status of middle cerebral artery aneurysms (0.85). CONCLUSIONS: This preliminary study suggests that the spatiotemporal characteristics of flow vortices within MCA aneurysms are of value to improve the differentiation of ruptured aneurysms from unruptured ones.

Screening Mentally Retarded Children for Inborn Errors of Metabolism.

BACKGROUND: Most inborn errors of metabolism result in mental retardation and death due to accumulation of abnormal metabolites in the tissues. The presence of abnormal metabolites in the urine of mentally retarded individuals has been used worldwide for detection of inborn errors of metabolism. The purpose of the study is to determine the prevalence of inborn error of metabolism in mentally retarded children. METHODS: Random urine samples were collected from mentally retarded children at two institutes in Kathmandu, and also from 60 normal children from Duwakot, Nepal after obtaining consent from their parents. Urine was then tested for the presence of amino acids, keto-acids, mucopolysaccharides, fructose, glucose and protein using simple qualitative color reactions in the laboratory. RESULTS: The tests detected eight cases of Phenylketonuria, which turned out to be false positive on paper chromatography. Three cases of presence of ketone bodies (acetoacetate), ten cases of α-ketoaciduria, two cases of mucopolysaccharidosis and twelve cases of fructosuria amongst the sixty-two urine samples were also found. CONCLUSIONS: Certain aminoacidurias, ketoacidurias and mucopolysaccharidoses might be present in the Nepalese population. Within consideration of errors, the samples tested positive should be evaluated by a higher end method to confirm the utility of these simple and cheap chemical tests.

Large-volume blood patch to multiple sites in the epidural space through a single-catheter access site for treatment of spontaneous intracranial hypotension.

BACKGROUND AND PURPOSE: Spontaneous intracranial hypotension can be a therapeutic challenge to the treating physician. In this study, we present our experience with the administration of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site. MATERIALS AND METHODS: A retrospective review was conducted of patients with spontaneous intracranial hypotension who underwent a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site from 2010 to 2012. Patient demographic data, clinical charts, indications for treatment, radiographic images, procedure notes, and postprocedure hospital course were reviewed. RESULTS: Overall, 9 patients were identified who underwent 20 blood patch procedures. Patients were selected to undergo the large-volume procedure either because they had a failed site-directed epidural blood patch or if imaging demonstrated multiple possible leak sites. There were 6 women and 3 men, with an average age of 33.5 years. The mean volume of blood injected per procedure was 54.1 mL (median=55 mL; range=38-70 mL). All patients had an orthostatic headache as one of their presenting symptoms; 22% also presented with neurocognitive decline and behavioral changes; 89% of patients had improvement or resolution of their symptoms; and 80% of patients who had a previously failed site-directed epidural blood or fibrin glue patch improved with a large volume catheter-directed blood patch. CONCLUSIONS: Our experience supports the use of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site for the treatment of spontaneous intracranial hypotension. Additionally, our results indicate a role for this procedure in refractory cases of spontaneous intracranial hypotension.

Spinal dural arteriovenous fistulas: clinical experience with endovascular treatment as a primary therapy at 2 academic referral centers.

BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas are a rare entity that, if left untreated, can lead to considerable morbidity with progressive spinal cord symptoms. The aim of this study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas that were primarily treated with endovascular embolization. MATERIALS AND METHODS: A retrospective review was performed of all patients from 1997-2010 who underwent treatment at 2 academic referral centers for a spinal dural arteriovenous fistula. Follow-up was performed by clinical examination, and functional status was measured by use of the Aminoff-Logue Disability Scale, McCormick classification grading, and mRS scores. The nonparametric Wilcoxon signed rank test was used to compare pretreatment and posttreatment Aminoff-Logue Disability Scale gait and micturition scores, McCormick classification grading, and mRS scores. P values < .05 were considered significant. RESULTS: A total of 38 patients were included. Five patients (2 endovascular, 3 surgical) were lost to follow-up and therefore were excluded from the analysis, 29 patients were initially treated from an endovascular approach (9 Onyx, 20 cyanoacrylate), and 4 patients were treated from a standard surgical approach. Five patients in the endovascular group subsequently underwent surgery for various reasons. The clinical improvements in the Aminoff-Logue Disability Scale gait and micturition scores, McCormick classification grading, and the mRS scores were statistically significant (P < .05, Wilcoxon signed rank test). CONCLUSIONS: We conclude that endovascular treatment of spinal dural arteriovenous fistulas can result in good clinical outcomes. Surgery remains the treatment of choice when safe embolization of the proximal radicular draining vein cannot be obtained or because the shunting artery of the spinal dural arteriovenous fistula also supplies the anterior spinal, posterior spinal, or a radiculomedullary artery.

Preliminary experience with the percutaneous embolization of juvenile angiofibromas using only ethylene-vinyl alcohol copolymer (Onyx) for preoperative devascularization prior to surgical resection.

BACKGROUND AND PURPOSE: Juvenile angiofibromas are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss. Our purpose was to evaluate the extent of angiographic devascularization and intraoperative blood loss by using only Onyx for percutaneous juvenile angiofibroma tumor embolization. MATERIALS AND METHODS: We reviewed the clinical records and preoperative and postoperative imaging studies of a consecutive series of 9 patients with juvenile angiofibromas who were treated with preoperative embolization with direct percutaneous injection of Onyx followed by resection from a standard open surgical or endoscopic approach. RESULTS: Two Fisch type I, 1 Fisch type II, 5 Fisch type IIIa, and 1 Fisch type IVa tumor were treated. Complete devascularization was achieved in all cases percutaneously with only Onyx. There were no complications. The average intraoperative blood loss was 567.7 mL (range, 10-1700 mL). An average of 2.2 needles (range, 1-5 needles) was placed into the tumor. An average of 14.6 mL of Onyx (range, 2-25 mL) was injected into each tumor. Four Fisch type IIIa tumors were removed completely from only an ENE approach. CONCLUSIONS: Presurgical direct percutaneous embolization of a juvenile angiofibroma with only EVOH before surgical resection is safe and feasible. Our preliminary experience suggests that Onyx may offer a higher degree of devascularization compared with other embolic agents. This may facilitate an easier surgical resection with lower blood loss.

Acute life-threatening hemorrhage in patients with head and neck cancer presenting with carotid blowout syndrome: follow-up results after initial hemostasis with covered-stent placement.

BACKGROUND AND PURPOSE: CSP in patients with HNC presenting with CBS can provide immediate hemostasis to prevent exsanguination. We evaluated the safety and efficacy of CSP to control acute life-threatening hemorrhage in patients with HNC presenting with CBS. MATERIALS AND METHODS: We retrospectively reviewed 10 patients (7 men, 3 women; mean age, 59 years) with HNC presenting with acute life-threatening hemorrhage from CBS that was treated with CSP. We studied patient demographics, presentations, procedures, initial and delayed complications, and technical and clinical outcomes on follow-up. RESULTS: All patients achieved immediate hemostasis following CSP. Periprocedural complications consisted of groin hematomas (n=2), acute limb ischemia requiring thrombectomy, and an asymptomatic temporal lobe hemorrhage. Imaging and clinical follow-up were available for a mean of 17.7 months (range, 1-60 months). Two patients remained asymptomatic with a patent stent and no evidence of rebleeding at 17 and 21 months, respectively. Recurrent hemorrhages requiring retreatment were encountered in 3 patients secondary to stent infections (30%) at mean duration of 8 months. Neurologic morbidity resulted from stent thrombosis and stroke at 8 months in a single patient. Mortality was unrelated to CSP but was a result of palliative hospice care (n=3) at a mean of 2 months or natural disease progression (n=1) with documented patency of the stent at 6 months. CONCLUSIONS: Acute life-threatening hemorrhage from CBS related to advanced HNC can be safely and effectively treated with CSP. However, potential delayed ischemic or infectious complications are common in the exposed or infected neck.

Intracranial endovascular balloon test occlusion-indications, methods, and predictive value.

The balloon test occlusion is one method by which surgeons evaluate whether a patient will be able to tolerate permanent occlusion of an extracranial or intracranial vessel. This article discusses the indications, methods, predictive value, and complications of the balloon test occlusion. It also briefly describes the Wada test in the context of preoperative evaluation of patients who are candidates for temporal lobectomy.

Human endothelin-1 clearance kinetics revealed by a radiotracer technique.

Levels of endothelin-1 (ET-1) are elevated in many disease states, although its total body kinetics of elimination are poorly understood. Therefore, it remains uncertain whether the presence of elevated levels of ET-1 in the setting of disease are secondary to changes in production or clearance or some combination thereof. Using a 125I-labeled ET-1 infusion technique, the volume of distribution and kinetics of clearance of endothelin were described in five normal volunteers. Heart rate, blood pressure, right atrial pressure, and arterial blood samples for the counting of 125I and the measurement of ET-1 were obtained at multiple time points before and up to 45 h after the start of the infusion. The radiotracer infusion had no effect on heart rate, blood pressure, right atrial pressure, or endogenous ET-1 levels. ET-1 clearance was best described by a three-compartment model, which revealed that ET-1 has a much longer terminal half-life and volume of distribution than was previously reported. This suggests extensive uptake of ET-1 in various organ systems and slow clearance. These new findings have important implications for the understanding of the pathophysiology of ET-1 in disease states as well as for the understanding and development of ET-1 receptor blockers and endothelin-converting enzyme inhibitors.

Chronic endothelin-1 blockade preserves myocardial contractility in dilated cardiomyopathy.

Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated cardiac muscle strips. ET-1 levels are elevated in congestive heart failure (CHF). We investigated the effects of ET-1 on contractility and cardiac relaxation (lusitropy) of the intact healthy murine heart and myocarditic/cardiomyopathic heart by chronic oral treatment with a mixed ETA/ETB blocker SB217242. Chronic ET-1 blockade of normal hearts resulted in depression of contractility and lusitropy of the normal heart but preservation and enhancement of contractility and lusitropy in myocarditic animals, in which ET-1 cardiac content is elevated. This suggests that ET-1 is important in the basal contractility and relaxation of the normal heart but that its chronic elevation in CHF causes impairment of cardiac systolic and diastolic performance.

Right heart pulmonary embolism in transit: a review of therapeutic considerations.

Two patients with pulmonary emboli and right heart masses detected on echocardiography are described. One patient underwent successful surgical embolectomy and the other was successfully treated with intravenous thrombolysis. Both were alive and well at six months' follow-up. The presence of a right heart clot in the setting of pulmonary emboli carries a very high mortality rate and warrants urgent therapy, which may include anticoagulation, thrombolysis or surgical embolectomy. Because limited information is available, therapy must be individualized based on patient characteristics, clot location and local expertise. The pertinent literature is reviewed and relevant issues in decision making are discussed.

Effects of metals on early life stages of the brine shrimp, Artemia: a developmental toxicity assay.

The need for simple, fast and inexpensive tests to study metal pollution in the marine environment has become more pressing as utilization of coastal waters increases. To address this concern, the influence of four metals, cupric sulfate, lead nitrate, zinc sulfate and nickel sulfate, on emergence and hatching of the brine shrimp, Artemia, has been assessed. Occurrence of these easily recognized developmental milestones provides a convenient method to assay metal effects on development. Copper and lead were about equally toxic, reducing the rate and extent of Artemia development at or below concentrations of 0.1 microM. Zinc was somewhat less toxic than copper and lead, while nickel was the least toxic. Emerging Artemia are much more sensitive to metals than are larvae and adults. Furthermore, in contrast to results obtained with larvae and adults, the toxicity of lead is high when prelarval stages are considered. It is apparent from the findings that use of early stages of Artemia is an alternative to the examination of slower growing animals for the study of metal pollution in coastal marine waters.

Toxicity of organic mercury compounds to the developing brine shrimp, Artemia.

Mercury can be coupled to a wide variety of organic compounds but there is limited information concerning the influence of such substitutions on the toxicity of mercury within the marine environment. We therefore determined the effects of six organomercuries on the emergence and hatching of the brine shrimp, Artemia. The relative toxicities of the organic mercuries were unaffected by the ability of the compounds to ionize, whereas the sizes of the compounds appeared to be important. Thus, brine shrimp were equally sensitive to five of the organic mercuries while diphenylmercury, the largest of the organic mercuries tested, was the least toxic. In the presence of 0.1 microM diphenylmercury the final amount of hatching was similar to that in the absence of metal but in this situation there was an easily measured reduction in the rate of development. By determining the rates of emergence and hatching it is apparent that Artemia are adversely affected by organic mercuries at concentrations less than 0.1 microM, the lowest level examined in this study. The work extends our earlier findings with cadmium and zinc, supporting the proposal that Artemia is an excellent alternative to more complex, slow-growing animals for the study of biochemical/physiological aspects of marine pollution.